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Institute: Institute for Heart Research

Study of endogenous compensatory mechanisms effective against energy deficiency in pathologycally loaded myocardium: Innovative approaches in experimental cardioprotection.
Kompenzačné ochranné mechanizmy ako účinný nástroj voči zvýšenej energetickej deficiencii patologicky zaťaženého myokardu: Výhodná perspektíva v modernej experimentálnej kardioprotekcii.
Program: SRDA
Project leader: Ing. Ferko Miroslav PhD.
Annotation:Research on field of compensatory mechanisms appears to be promising method for endogenous protection in pathologically loaded myocardium under condition of increased energy demands. The project aims to contribute to the knowledge in the field of experimental cardiology and point to new, alternative cardioprotective procedures against ischemia-reperfusion injury. It is necessary to study the protective signaling pathways, propose potential cardiomarkers and identify positive functional changes observed at the level of cardiac mitochondria and heart its self for comprehensive understanding of the onset and progression of mechanisms of endogenous myocardial protection leading to effective compensation against energy deficiency in ischemia/reperfusion injury. Several approaches utilize processes of endogenous protection to achieve cardioprotection, such as ischemic and pharmacological preconditioning, clinically applicable „remote“ ischemic preconditioning (RIP) as well as experimental streptozotocine-induced diabetes mellitus in acute state. Coexistence of several comorbidities (hypercholesterolaemia, hypertension) suppress mechanisms of cell signaling involved in protective effect of ischemic preconditioning that promotes necrotic and apoptotic processes in the myocytes during ischemiareperfusion challenge and also reduces energy production. With respect to bioenergetics and the role of mitochondria involved in the execution phase of cardioprotection as a common mechanism in various types of adaptive phenomena, the information is scarse up to date. It is expected that the project will help to characterize the changes caused by functional remodeling of the mitochondrial membrane, and provide a new and currently absenting information on regulation of mechanisms against increased enegetic demands resulting in myocardial survival.
Duration: 1.7.2016 - 30.6.2020

Bioenergetic aspects of myocardial protection by means of remote ischemic preconditioning. The role of cardiac mitochondria
Bioenergetické aspekty ochrany myokardu pomocou remote ischemického preconditioningu. Úloha srdcových mitochondrií
Program: VEGA
Project leader: Ing. Ferko Miroslav PhD.
Annotation:Any sufficiently strong challenge induced by physiological or pathological stimuli leads to myocardial changes that can be considered as abnormal. These changes partially reflect endogenous protective processes. Pathological stimuli triggering the endogenous protection are hypoxia, ischemia, diabetes mellitus and hypertension. Cardioprotective approaches involve pharmacological and ischemic preconditioning (IP) as well as clinically applicable form of IP, so called remote ischemic preconditioning (RIP). Numerous mechanisms of RIP induction and effects have been investigated. Still, the character of the signals from the site of RIP leading to target structures in the heart is not elucidated. Little is known also with respect to bioenergetics aspects and role of cardiac mitochondria in RIP induced cardioprotection. The aim of this project is to contribute to elucidation of the molecular mechanisms of RIP and role of mitochondria in the signaling processes of RIP and heart adaptation to hypoxia and ischemia.
Duration: 1.1.2015 - 31.12.2017

Hypoxia in the prevention of heart failure in rats and its influence in various stages of heart failure: Characteristics of functional, structural and molecular changes.
Hypoxia ako prevencia zlyhávania srdca potkana a jej vplyv v rôznych fázach zlyhávania: Charakteristika funkčných, štrukturálnych a molekulárnych zmien.
Program: VEGA
Project leader: Mgr. Farkašová Veronika PhD
Annotation:Ischemic heart disease and hypertension are major ailments leading to heart remodeling, cardiac hypertrophy, and subsequent heart failure (HF). Progression of HF depends not only on the extent of ischemic injury, but also on the presence of lifestyle risk factors. Cardioprotective adaptive interventions can slow the progression of cardiac hypertrophy to HF, but their effectiveness is adversely affected by cardiovascular comorbidities and by aging. The project aims are to study the possibility of reactivating adaptative potential in pathologically remodelled myocardium by modulating the intensity and timing of adaptive stimuli. We will examine the effects of intermittent hypoxia applied prior to the pathological stimulus and in various stages of development of hypertrophy and HF, focusing on functional and structural changes in the myocardium. We will aim to characterize the specific signaling pathways associated with the origin and development of HF and hypoxia-induced changes in intracellular signaling.
Duration: 1.1.2017 - 31.12.2019

Matrix-metalloproteinases, microRNAs and deformability of erythrocytes as a novel diagnostic and predictive biomarkers of heart failure
Matrix metaloproteinázy, microRNAs a deformabilita erytrocytov - nové diagnostické a prognostické biomarkery srdcového zlyhávania
Program: VEGA
Project leader: RNDr. Barteková Monika PhD.
Duration: 1.1.2014 - 31.12.2017

Molecular mechanisms involved in the effects of doxorubicin in rats with developed hypertension and ways of modulation of of these effects of doxorubicin by quercetin.
Molekulárne mechanizmy zahrnuté v účinkoch doxorubicínu u zvierat s rozvinutou hypertenziou a možnosti ovplyvnenia účinkov doxorubicínu pôsobením kvercetínu.
Program: VEGA
Project leader: RNDr. Barančík Miroslav DrSc.
Duration: 1.1.2015 - 31.12.2017

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Možná duálna funkcia P-glykoproteínu pri viacliekovej rezistencii leukemických buniek: efluxná pumpa a regulačný proteín.
Program: SRDA
Project leader: RNDr. Barančík Miroslav DrSc.
Duration: 1.7.2014 - 30.6.2018

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Nové molekulárne mechanizmy poškodenia kardiovaskulárneho systému ionizujúcim žiarením a možnosti jeho cielenej medikamentóznej prevencie.
Program: VEGA
Project leader: D.h.c.,Prof., MUDr. Slezák Ján DrSc., FIACS
Duration: 1.1.2015 - 31.12.2017

Protection of mechanisms modulating endothelial permeability in the heart.
Ochrana mechanizmov modulujúcich permeabilitu endotelu v srdci.
Program: VEGA
Project leader: RNDr. Okruhlicová Ľudmila CSc.
Duration: 1.1.2016 - 31.12.2019

Protection of the heart from maladaptive extracellular matrix remodeling and searching the mechanisms of its regression.
Ochrana srdca pred maladaptívnou remodeláciou extracelularnej matrix a skúmanie mechanizmov jej regresie.
Program: VEGA
Project leader: RNDr. Szeiffová Bačová Barbara PhD.
Annotation:Heart diseases are accompanied by exracellular matrix remodeling and fibrosis resulting in development of heart failure and malignant arrhythmias. Fibrosis is a major medical problem without existing cure. However, there are cardioprotective compounds that exhibit antifibrotic effects but underlying mechanisms are poorly understood. This project is aimed to characterize key factors implicated in profibrotic signaling in rats suffering from hypertension, diabetes, hypothyroidism and post-infarction injury and to determine targets of examined pharmacological and nonpharmacological compounds. This approach should reveal signaling pathways and factors, whose modulation could hamper or reverse fibrosis. It is expected that findings of this preclinical study may outline design of clinical trials how to protect the heart from its dysfunction by non-invasive way.
Duration: 1.1.2015 - 31.12.2018

PROTECTION OF THE HEART IN SITUATIONS OF INCREASED PRODUCTION OF OXYGEN FREE RADICALS: RADIATION AND REPERFUSION INJURY
OCHRANA SRDCA V SITUÁCIÁCH ZVÝŠENEJ PRODUKCIE VOĽNÝCH KYSLÍKOVÝCH RADIKÁLOV: RADIAČNÉ A REPERFÚZNE POŠKODENIE
Program: SRDA
Project leader: D.h.c.,Prof., MUDr. Slezák Ján DrSc., FIACS
Annotation:According to statistics, cardiovascular and cancer are the main cause of more than 93% of the global morbidity and mortality. One of the most used methods to treat patients with cancer is radiotherapy, which uses ionizing radiation. Ionizing radiation damages the cancer cells, leading to their apoptosis and to potential patient recovery. However, during irradiation of cancer cells may also occur unintended exposure of surrounding healthy tissue, which in turn can cause serious health complications including radiation-induced heart disease. Ionising radiation acts directly on the DNA of cells, or indirectly through the formation of free radicals, which then damage the individual organelles of cells or DNA. Production of oxygen free radicals, which in addition have a signaling function, at higher concentrations have toxic effects on all parts of the heart and blood vessels, is a common denominator of both ionizing radiation and inflammation, as well as ischemic and reperfusion injury. Therefore, research in this field, and finding novel suitable materials which can positively influence the effects of over
Duration: 1.7.2016 - 30.6.2020

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Relevancia nekroptózy v odumieraní myokardiálneho tkaniva v dôsledku rôznych typov poškodenia: vplyv na excitačno-kontrakčné prepojenie.
Program: VEGA
Project leader: Ing. Ferko Miroslav PhD.
Duration: 1.1.2016 - 31.12.2019

Investigation of regulatory mechanisms of cardiac cell-cell communication for targeted protection from heart failure.
Skúmanie regulačných mechanizmov medzibunkovej komunikácie v srdci pre cielenú ochranu pred jeho funkčným zlyhaním.
Program: VEGA
Project leader: RNDr. Tribulová Narcisa DrSc.
Annotation:Cardiac cell-to-cell communication via gap junction connexin (Cx) channels is essential for synchronised heart function. While disorders in expression, distribution and phosphorylation of Cx in of both human and animal heart diseases promote occurrence of malignant arrhythmias and heart failure. We hypothesize that targeted modulation of Cx channel function by exogenous and endogenous compounds may be a promising approach to protect proper heart function. Aim of this project is to elucidate mechanisms implicated in regulation of Cx43-mediated cardiac cell-to-cell communication in healthy and diseased heart. Research findings should enhance knowledge of cardiologists in this field and challenge the realization of clinical trials supporting novel approaches in prevention and/or treatment of heart diseases to fight sudden cardiac death.
Duration: 1.1.2016 - 31.12.2019

Study of the clinically relevant forms of preconditioning as an alternative method of myocardial protection against acute ischemia in the organism challenged with civilization diseases
Štúdium klinicky využiteľných foriem preconditioningu ako alternatívnej metódy ochrany myokardu pred akútnou ischémiou v organizme zaťaženom civilizačnými ochoreniami
Program: VEGA
Project leader: MUDr. Ravingerová Táňa DrSc., FIACS
Annotation:Hypertension, metabolic disorders, sex and aging have a negative impact on the adaptive mechanisms of innate cardioprotection and alter heart survival upon acute ischemia/reperfusion (I/R). These comorbidities suppress the mechanisms of cell signaling involved in protective effects of ischemic preconditioning (PC) and accelerate necrotic and apoptotic processes during I/R, reduce energy production and contribute to enhanced arrhythmogenesis. The project is aimed to investigate the possiblities to restore adaptive potential in the pathologically altered myocardium including aged heart by means of modulation of the intensity and forms of adaptive stimuli. Effects of clinically relevant forms of PC: „remote“ PC of the heart induced by ischemia of the distant organ and its pharmacological simulations by drugs regulating energy metabolisms and involved in the mechanisms of PC, as well as their genomic and non-genomic effects including the impact on mitochondrial function and apoptotic cascade will be investigated
Duration: 1.1.2015 - 31.12.2017

The role of extracellular vesicles in inter-organ communication related to remote cardioprotection
Úloha extracelulárnych vezikúl v medziorgánovej komunikácii zahrnutej v kardioprotekcii na diaľku (remote conditioning).
Program: VEGA
Project leader: RNDr. Barteková Monika PhD.
Annotation:Inter-organ communication plays a crucial role in cardioprotection induced by an ischemic (or other) insult on remote organ to the heart, called remote ischemic preconditioning, or remote conditioning in general. Extracellular vesicles (EVs) are membrane-bound structures secreted by a wide range of mammalian cell types that can be secreted and specifically taken up by other cells. Since EVs contain a high concentration of RNAs and proteins, they are of a high interest as potential mediators of remote cardioprotection, and thus for inter-organ signal transfer mechanisms in general. Revealing the role of EVs in communication between different cells and organs as well as identifying substances transported by EVs to be potential mediators of cardioprotection as the main goal of the current project could lead to better understanding of remote cardioprotection and inter-organ communication in general, and rise up new potential targets of therapy of heart ischemia.
Duration: 1.1.2016 - 31.12.2019

The total number of projects: 14